PMID- 22916248
OWN - NLM
STAT- MEDLINE
DCOM- 20130116
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Transcript and protein analysis reveals better survival skills of 
      monocyte-derived dendritic cells compared to monocytes during oxidative stress.
PG  - e43357
LID - 10.1371/journal.pone.0043357 [doi]
LID - e43357
AB  - BACKGROUND: Dendritic cells (DCs), professional antigen-presenting cells with the 
      unique ability to initiate primary T-cell responses, are present in 
      atherosclerotic lesions where they are exposed to oxidative stress that generates 
      cytotoxic reactive oxygen species (ROS). A large body of evidence indicates that 
      cell death is a major modulating factor of atherogenesis. We examined antioxidant 
      defence systems of human monocyte-derived (mo)DCs and monocytes in response to 
      oxidative stress. METHODS: Oxidative stress was induced by addition of 
      tertiary-butylhydroperoxide (tert-BHP, 30 min). Cellular responses were evaluated 
      using flow cytometry and confocal live cell imaging (both using 
      5-(and-6)-chloromethyl-2,7-dichlorodihydrofluorescein diacetate, CM-H(2)DCFDA). 
      Viability was assessed by the neutral red assay. Total RNA was extracted for a 
      PCR profiler array. Five genes were selected for confirmation by Taqman gene 
      expression assays, and by immunoblotting or immunohistochemistry for protein 
      levels. RESULTS: Tert-BHP increased CM-H(2)DCFDA fluorescence and caused cell 
      death. Interestingly, all processes occurred more slowly in moDCs than in 
      monocytes. The mRNA profiler array showed more than 2-fold differential 
      expression of 32 oxidative stress-related genes in unstimulated moDCs, including 
      peroxiredoxin-2 (PRDX2), an enzyme reducing hydrogen peroxide and lipid 
      peroxides. PRDX2 upregulation was confirmed by Taqman assays, immunoblotting and 
      immunohistochemistry. Silencing PRDX2 in moDCs by means of siRNA significantly 
      increased CM-DCF fluorescence and cell death upon tert-BHP-stimulation. 
      CONCLUSIONS: Our results indicate that moDCs exhibit higher intracellular 
      antioxidant capacities, making them better equipped to resist oxidative stress 
      than monocytes. Upregulation of PRDX2 is involved in the neutralization of ROS in 
      moDCs. Taken together, this points to better survival skills of DCs in oxidative 
      stress environments, such as atherosclerotic plaques.
FAU - Van Brussel, Ilse
AU  - Van Brussel I
AD  - Laboratory of Cellular and Molecular Cardiology, University of Antwerp, Wilrijk, 
      Antwerp, Belgium. ilse.vanbrussel@ua.ac.be
FAU - Schrijvers, Dorien M
AU  - Schrijvers DM
FAU - Martinet, Wim
AU  - Martinet W
FAU - Pintelon, Isabel
AU  - Pintelon I
FAU - Deschacht, Maartje
AU  - Deschacht M
FAU - Schnorbusch, Kathy
AU  - Schnorbusch K
FAU - Maes, Louis
AU  - Maes L
FAU - Bosmans, Johan M
AU  - Bosmans JM
FAU - Vrints, Christiaan J
AU  - Vrints CJ
FAU - Adriaensen, Dirk
AU  - Adriaensen D
FAU - Cos, Paul
AU  - Cos P
FAU - Bult, Hidde
AU  - Bult H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120815
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Cells, Cultured
MH  - Dendritic Cells/*metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Monocytes/*cytology
MH  - Oxidative Stress/genetics/*physiology
MH  - Reactive Oxygen Species/metabolism
PMC - PMC3419731
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/24 06:00
MHDA- 2013/01/17 06:00
PMCR- 2012/08/15
CRDT- 2012/08/24 06:00
PHST- 2011/10/20 00:00 [received]
PHST- 2012/07/23 00:00 [accepted]
PHST- 2012/08/24 06:00 [entrez]
PHST- 2012/08/24 06:00 [pubmed]
PHST- 2013/01/17 06:00 [medline]
PHST- 2012/08/15 00:00 [pmc-release]
AID - PONE-D-11-20936 [pii]
AID - 10.1371/journal.pone.0043357 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e43357. doi: 10.1371/journal.pone.0043357. Epub 2012 Aug 15.